Head and Eye Movements Reveal Compensatory Strategies for Acute Binaural Deficits During Sound Localization.

The present study aimed to define use of head and eye movements during sound localization in children and adults to: (1) assess effects of stationary versus moving sound and (2) define effects of binaural cues degraded through acute monaural ear plugging. Thirty-three youth (MAge = 12.9 years) and seventeen adults (MAge = 24.6 years) with typical hearing were recruited and asked to localize white noise anywhere within a horizontal arc from -60° (left) to +60° (right) azimuth in two conditions (typical binaural and right ear plugged). In each trial, sound was presented at an initial stationary position (L1) and then while moving at ∼4°/s until reaching a second position (L2). Sound moved in five conditions (±40°, ±20°, or 0°). Participants adjusted a laser pointer to indicate L1 and L2 positions. Unrestricted head and eye movements were collected with gyroscopic sensors on the head and eye-tracking glasses, respectively. Results confirmed that accurate sound localization of both stationary and moving sound is disrupted by acute monaural ear plugging. Eye movements preceded head movements for sound localization in normal binaural listening and head movements were larger than eye movements during monaural plugging. Head movements favored the unplugged left ear when stationary sounds were presented in the right hemifield and during sound motion in both hemifields regardless of the movement direction. Disrupted binaural cues have greater effects on localization of moving than stationary sound. Head movements reveal preferential use of the better-hearing ear and relatively stable eye positions likely reflect normal vestibular-ocular reflexes.

Hearing loss caused by CMV infection is correlated with reduced endocochlear potentials caused by strial damage in murine models.

Congenital cytomegalovirus (CMV) infection is a significant cause of neonatal hearing loss. However, at the cochlear level, the anatomical lesions and pathophysiological mechanisms that underlie hearing loss are still not clearly understood. In murine models of CMV infection, we have observed early damage to the capillary networks in stria vascularis, as well as hearing loss manifested in ABR threshold elevations. Our experimental hypothesis is that strial damage causes a reduced endocochlear potential (EP) resulting in impaired haircell activation and consequent hearing loss. We have studied strial damage, EP, and ABR threshold elevations in two mouse models (BALB/c and C57BL6 strains) infected with murine CMV. Neonatal (P3) pups were inoculated with murine CMV (2µl of 200pfu) by intra cerebral injection. Control mice were saline injected. At 6 weeks, ABR thresholds to tonal stimuli at 8, 16 and 32 kHz were determined for each ear. At 8 weeks a sub-group of treated and control animals was prepared for study of cochlear capillary networks using scanning electron microscopy of corrosion cast specimens. In a second group, at 8 weeks, EP measurements from both cochleas were made. We report that in both mouse strains, CMV infection caused capillary loss in the stria vascularis, initially at the cochlear apex, and extending to lower cochlear turns in some subjects. After CMV infection, in both BALB/c and C57BL6 mice, reduced EPs and ABR threshold elevations were observed, and there was a within-animal correlation between loss of EP and ABR threshold elevations across the sound frequencies tested. These results suggest that CMV induced damage to stria vascularis results in EP reduction that is correlated with ABR threshold elevations. Extrapolating to the human condition, we suggest that strial damage and its physiological consequences may contribute to the initial hearing loss in congenital CMV infection. The early involvement of cochlear capillary damage may encourage a focus on therapeutic interventions that can prevent vascular damage, or subsequently promote vascular healing or angiogenesis.

Ultrasonic bone removal from the ossicular chain affects cochlear structure and function.

INTRODUCTION: Ultrasonic bone removal devices (UBD) are capable of cutting through bony tissue without injury to adjacent soft tissue. The feasibility and safety of using this technology for removal of bone from an intact ossicular chain (as might be required for otosclerosis or congenital fixation) was investigated in an animal model. METHODS: This was a prospective animal study conducted on seven anesthetised adult chinchillas. An UBD was used to remove bone from the malleus head in situ. Pre and post-operative distortion product otoacoustic emission (DPOAE) levels and auditory brainstem response (ABR) thresholds were recorded. Scanning electron microscopy (SEM) was used to assess cochlear haircell integrity. RESULTS: Precise removal of a small quantity of bone from the malleus head was achieved by a 30s application of UBD without disruption of the ossicular chain or tympanic membrane. DPOAEs became undetectable after the intervention with signal-to-noise ratios (SNR) < 5 dB SPL in all ears. Furthermore, ABR thresholds were elevated > 85 dB SPL in 13 ears. SEM showed significant disruption of structural integrity of the organ of Corti, specifically loss and damage of outer haircells. CONCLUSIONS: Although UBD can be used to reshape an ossicle without middle ear injury, prolonged contact with the ossicular chain can cause structural and functional injury to the cochlea. Extensive cochlea pathology was found, but we did not investigate for recovery from any temporary threshold shift. In the authors' opinion, further study should be undertaken before consideration is given to use of the device for release of ossicular fixation.

Synthetic Simulator for Surgical Training in Tracheostomy and Open Airway Surgery.

OBJECTIVE(S): To create and validate a synthetic simulator for teaching tracheostomy and laryngotracheal reconstruction (LTR) using anterior costal cartilage and thyroid ala cartilage grafts. METHODS: A late adolescent/adult neck and airway simulator was constructed based on CT scans from a cadaver and a live patient. Images were segmented to create three-dimensional printed molds from which anatomical parts were casted. To evaluate the simulator, expert otolaryngologists - head and neck surgeons performed tracheostomy and LTR using anterior costal cartilage and thyroid ala cartilage grafts on a live anesthetized porcine model (gold standard) followed by the synthetic simulator. They evaluated each model for face validity (realism and anatomical accuracy) and content validity (perceived effectiveness as a training tool) using a five-point Likert scale. For each expert, differences for each item on each simulator were compared using Wilcoxon Signed-Rank tests with Sidak correction. RESULTS: Nine expert faculty surgeons completed the study. Experts rated face and content validity of the synthetic simulator an overall median of 4 and 5, respectively. There was no difference in scores between the synthetic model and the live porcine model for any of the steps of any of the surgical procedures. CONCLUSION: The synthetic simulator created for this study has high face and content validity for tracheostomy and LTR with anterior costal cartilage and thyroid ala cartilage grafts and was not found to be different than the live porcine model for these procedures. LEVEL OF EVIDENCE: 5 Laryngoscope, 131:E2378-E2386, 2021.

Does riboflavin depletion cause auditory neuropathy spectrum disorder in at risk neonates?

We present a new hypothesis for the pathogenesis of auditory neuropathy spectrum disorder (ANSD) in at risk neonates involving depletion of riboflavin. The association between neonatal hyperbilirubinemia and ANSD is well recognized, yet causation has not been proven. The risk of ANSD does not correlate clearly with severity of hyperbilirubinemia and ASND only occurs in a small proportion of hyperbilirubinemic neonates. Additional, perhaps co-dependent, factors are therefore likely to be involved in pathogenesis. The metabolism of bilirubin consumes riboflavin and levels of riboflavin are depleted further by phototherapy. The neonate may also be deficient in riboflavin secondary to maternal deficiency, and reduced intake or impaired absorption. We propose that riboflavin depletion may be a significant contributor to development of ANSD in at risk neonates. The basis of this hypothesis is the recent recognition that impairment of riboflavin metabolism caused by genetic mutations (SLC52A2 or AIMF1) also causes ANSD.

Live porcine model for surgical training in tracheostomy and open-airway surgery.

OBJECTIVES/HYPOTHESIS: To evaluate the validity of a live porcine model for surgical training in tracheostomy and open-airway surgery. STUDY DESIGN: Prospective observational study. METHODS: Eleven expert otolaryngologists-head and neck surgeons rated a live porcine model's realism/anatomical accuracy (face validity) and perceived effectiveness as a training tool (content validity) for tracheostomy and laryngotracheoplasty using anterior costal cartilage and thyroid ala cartilage grafts using a 53-item post-trial questionnaire with a five-point Likert scale. RESULTS: Experts rated the face validity of the live porcine model a median (interquartile range [IQR]) of 4/5 (4-5) and the content validity a median (IQR) of 5/5 (4-5) for each surgical procedure. Overall, 91% strongly agreed or agreed that the simulator would increase trainee competency for tracheostomy and laryngotracheoplasty using costal cartilage graft, and 82% strongly agreed or agreed that it would increase trainee competency for laryngotracheoplasty using thyroid ala cartilage graft. CONCLUSIONS: The live porcine model has high face and content validity as a training tool for tracheostomy and laryngotracheoplasty using costal cartilage and thyroid ala cartilage grafts. This training model can help surgical trainees practice these complex, low-frequency procedures. LEVEL OF EVIDENCE: NA Laryngoscope, 130: 2063-2068, 2020.

Early Enzyme Replacement Therapy Improves Hearing and Immune Defects in Adenosine Deaminase Deficient-Mice.

Background: Inherited defects in adenosine deaminase (ADA) cause severe immune deficiency, which can be corrected by ADA enzyme replacement therapy (ERT). Additionally, ADA-deficient patients suffer from hearing impairment. We hypothesized that ADA-deficient (-/-) mice also exhibit hearing abnormalities and that ERT from an early age will improve the hearing and immune defects in these mice. Methods: Auditory brainstem evoked responses, organ weights, thymocytes numbers, and subpopulations, lymphocytes in peripheral blood as well as T lymphocytes in spleen were analyzed in ADA-/- and ADA-proficient littermate post-partum (pp). The cochlea was visualized by scanning electron microscopy (SEM). The effects of polyethylene glycol conjugated ADA (PEG-ADA) ERT or 40% oxygen initiated at 7 days pp on the hearing and immune abnormalities were assessed. Results: Markedly abnormal hearing thresholds responses were found in ADA-/- mice at low and medium tone frequencies. SEM demonstrated extensive damage to the cochlear hair cells of ADA-/- mice, which were splayed, short or missing, correlating with the hearing deficits. The hearing defects were not reversed when hypoxia in ADA-/- mice was corrected. Progressive immune abnormalities were detected in ADA-/- mice from 4 days pp, initially affecting the thymus followed by peripheral lymphocytes and T cells in the spleen. ERT initiated at 7 days pp significantly improved the hearing of ADA-/- mice as well as the number of thymocytes and T lymphocytes, although not all normalized. Conclusions: ADA deficiency is associated with hearing deficits and damage to cochlear hair cells. Early initiation of ERT improves the hearing and immune abnormalities.

Changes to Neural Activation Patterns (c-fos Labeling) in Chinchilla Auditory Midbrain following Neonatal Exposure to an Enhanced Sound Environment.

Sensory brain regions show neuroplastic changes following deficits or experimental augmentation of peripheral input during a neonatal period. We have previously shown reorganization of cortical tonotopic maps after neonatal cochlear lesions or exposure to an enhanced acoustic environment. Such experiments probe the cortex and show reorganization, but it is unclear if such changes are intrinsically cortical or reflect projections from modified subcortical regions. Here, we ask whether an enhanced neonatal acoustic environment can induce midbrain (inferior colliculus (IC)) changes. Neonatal chinchillas were chronically exposed to a 70 dB SPL narrowband (2 ± 0.25 kHz) sound stimulus for 4 weeks. In line with previous studies, we hypothesized that such exposure would induce widening of the 2 kHz tonotopic map region in IC. To probe c-fos expression in IC (central nucleus), sound-exposed and nonexposed animals were stimulated with a 2 kHz stimulus for 90 minutes. In sound-exposed subjects, we find no change in the width of the 2 kHz tonotopic region; thus, our hypothesis is not supported. However, we observed a significant increase in the number of c-fos-labeled neurons over a broad region of best frequencies. These data suggest that neonatal sound exposure can modify midbrain regions and thus change the way neurons in IC respond to sound stimulation.

Cochlear Nerve Aplasia with Detectable Olivocochlear Efferent Function: A Distinct Presentation of Auditory Neuropathy Spectrum Disorder.

BACKGROUND: Cochlear nerve aplasia (CNA) may present with features of auditory neuropathy spectrum disorder (ANSD), having detectable otoacoustic emissions (OAE) but profound hearing loss. We propose that some children with CNA have a distinct form of afferent ANSD in which efferent cochlear nerve function can be detected using contralateral suppression of OAE. METHODS: Children were prospectively enrolled with MRI and auditory brainstem response evidence of unilateral CNA, a normal contralateral ear, and detectable OAE bilaterally. Distortion product OAE (DPOAE) levels were recorded in real time with default primary tone settings: frequency (f)2 = 4.5 kHz and f2/f1 = 1.22 kHz, with level (L)1 = 65 dB SPL and L2 = 55 dB SPL. Recordings were made over 2 min with simultaneous application of an intermittent contralateral broadband noise (CBBN) stimulus at 60 dB SPL. RESULTS: Three girls, aged 4.5, 7, and 8 years, participated. Suppression of DPOAE of 0.15-1.3 dB was detected in all 3 ears with CNA in response to CBBN stimulation. No response was detected in the normal ears. CONCLUSIONS: Children with unilateral ANSD can have normal efferent cochlear nerve function despite MRI evidence of ipsilateral CNA. The importance of these findings for newborn hearing screening and cochlear implantation is discussed.

Cytomegalovirus (CMV) Infection Causes Degeneration of Cochlear Vasculature and Hearing Loss in a Mouse Model.

Cytomegalovirus (CMV) infection is one of the most common causes of congenital hearing loss in children. We have used a murine model of CMV infection to reveal functional and structural cochlear pathogenesis. The cerebral cortex of Balb/c mice (Mus musculus) was inoculated with 2000 pfu (plaque forming units) of murine CMV on postnatal day 3. At 6 weeks of age, cochlear function was monitored using auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measures. Histological assessment of cochlear vasculature using a corrosion cast technique was made at 8 weeks. Vascular casts of mCMV-damaged cochleas, and those of untreated control animals, were examined using scanning electron microscopy. We find very large variations in the degree of vascular damage in animals given identical viral injections (2000 pfu). The primary lesion caused by CMV infection is to the stria vascularis and to the adjacent spiral limbus capillary network. Capillary beds of the spiral ligament are generally less affected. The initial vascular damage is found in the mid-apical turn and appears to progress to more basal cochlear regions. After viral migration to the inner ear, the stria vascularis is the primary affected structure. We suggest that initial auditory threshold losses may relate to the poor development or maintenance of the endocochlear potential caused by strial dysfunction. Our increased understanding of the pathogenesis of CMV-related hearing loss is important for defining methods for early detection and treatment.

Midbrain Frequency Representation following Moderately Intense Neonatal Sound Exposure in a Precocious Animal Model (Chinchilla laniger).

Auditory brain areas undergo reorganization resulting from abnormal sensory input during early postnatal development. This is evident from studies at the cortical level but it remains unclear whether there is reorganization in the auditory midbrain in a species similar to the human, that is, with early hearing onset. We have explored midbrain plasticity in the chinchilla, a precocious species that matches the human in terms of hearing development. Neonatal chinchillas were chronically exposed to a 2 kHz narrowband sound at 70 dB SPL for 4 weeks. Tonotopic maps in inferior colliculus (central nucleus) were defined based on single neuron characteristic frequency. We hypothesized an overrepresentation of the 2 kHz region of the maps. However, we observed a significant decrease in the proportion of neurons dedicated to the 2 kHz octave band and also away from the exposure frequency at 8 kHz. In addition, we report a significant increase in low frequency representation (<1 kHz), again a change to tonotopic mapping distant to the 2 kHz region. Thus in a precocious species, tonotopic maps in auditory midbrain are altered following abnormal stimulation during development. However, these changes are more complex than the overrepresentation of exposure related frequency regions that are often reported.

How can the audiogram be more useful?

The Canadian Hearing and Auditory Research Translation (CHART) group is a newly formed taskforce to develop collaborative research initiatives. Initial discussions centered on diagnostic improvements for middle ear disease, auditory neuropathy spectrum disorder, tinnitus and presbycusis. Central to these discussions was the widely held view that the standard audiogram and its interpretation is inadequate to for describing many forms of hearing problems that we now recognize. This letter is designed to create awareness and to seek feedback from hearing healthcare professionals on their experience regarding the adequacy (or otherwise) of the audiogram in its present form.

Degeneration of stria vascularis in age-related hearing loss; a corrosion cast study in a mouse model.

Conclusion With age, in a mouse model, degenerative changes to the capillaries of the stria vascularis are observed. These range from a narrowing of vessel lumen to complete degeneration of strial vessels. Other vascular beds in the cochlea are relatively unchanged with age. Strial capillaries at the cochlear base are significantly more affected than those in mid-apical turns. Objectives Previous work suggests that age-related hearing loss is associated with degenerative changes to cochlear vasculature; the term strial presbyacusis is often cited. This study reports on vascular changes observed in a murine model of presbyacusis, analyzed using corrosion cast techniques. Methods A novel corrosion cast technique was developed to compare cochlear vasculature in control mice (non-presbycusic, CD1) and old (> 6 months) C57BL/6 animals. ABR measures indicated a significant age-related threshold elevation in the C57BL/6 mice. Cochlear vascular casts were imaged using scanning electron microscopy, and vessel degeneration was quantified by measuring capillary diameters. Results Corrosion casts of cochlear vasculature in 6-12 month old C57BL/6 mice reveal significant degeneration of stria vascularis. Other capillary beds (spiral ligament and the spiral limbus) appear unchanged. Comparison of strial capillary diameters reveals significantly more damage in basal/lower-turn regions compared with the cochlear mid-turn.

Partial corrosion casting to assess cochlear vasculature in mouse models of presbycusis and CMV infection.

Some forms of sensorineural hearing loss involve damage or degenerative changes to the stria vascularis and/or other vascular structures in the cochlea. In animal models, many methods for anatomical assessment of cochlear vasculature exist, each with advantages and limitations. One methodology, corrosion casting, has proved useful in some species, however in the mouse model this technique is difficult to achieve because digestion of non vascular tissue results in collapse of the delicate cast specimen. We have developed a partial corrosion cast method that allows visualization of vasculature along much of the cochlear length but maintains some structural integrity of the specimen. We provide a detailed step-by-step description of this novel technique. We give some illustrative examples of the use of the method in mouse models of presbycusis and cytomegalovirus (CMV) infection.

Auditory neuropathy spectrum disorder (ANSD) and cochlear implantation.

We discuss issues related to cochlear implantation in children with auditory neuropathy spectrum disorder (ANSD). We describe the varied nature of this disease category including the numerous potential causes of auditory neuropathy. The most prevalent etiology for infants with ANSD is associated with prolonged neonatal intensive care unit (NICU) stay. We discuss the potential contribution of cochlear hypoxia to this etiology. The second part of this review describes in detail our own experience at the Hospital for Sick Children in Toronto, with cochlear implantation of children diagnosed with ANSD. We outline the detection, diagnosis, and referral routes for our patients. We provide an overview of our "standard operation procedures" regarding candidacy, and discuss some of the special considerations that need to be applied to children with ANSD. This includes decisions to implant children with better audiometric thresholds that are standard in non-ANSD patients, concerns about the possibility of spontaneous remission and the appropriate timing of implantation. Finally we review an extensive published literature in outcomes after cochlear implantation (CI) in ANSD. This is not a systematic review but rather an exercise to distill out some important reoccurring themes and the general consensus of opinion to date. Our conclusion is that the hearing loss category ANSD, together with its numerous co-morbidities, is far too heterogeneous to make definitive statements about prognosis with CI.

On the biological plausibility of Wind Turbine Syndrome.

An emerging environmental health issue relates to potential ill-effects of wind turbine noise. There have been numerous suggestions that the low-frequency acoustic components in wind turbine signals can cause symptoms associated with vestibular system disorders, namely vertigo, nausea, and nystagmus. This constellation of symptoms has been labeled as Wind Turbine Syndrome, and has been identified in case studies of individuals living close to wind farms. This review discusses whether it is biologically plausible for the turbine noise to stimulate the vestibular parts of the inner ear and, by extension, cause Wind Turbine Syndrome. We consider the sound levels that can activate the semicircular canals or otolith end organs in normal subjects, as well as in those with preexisting conditions known to lower vestibular threshold to sound stimulation.

Excitatory and inhibitory tonotopic bands in chinchilla inferior colliculus revealed by c-fos immuno-labeling.

We describe in detail a reliable experimental protocol for c-fos immuno-labeling of patterns of neural activation in the chinchilla (chinchilla laniger). We report on resting-level neural activity in inferior colliculus (IC) of auditory midbrain, and on tonotopic bands present following 90 min of pure-tone sound stimulation. Neurons activated by 6-kHz sound stimulation lay ventro-medial to those activated at 2 kHz. This is consistent with the known tonotopic organization of IC, and verified in the present report by multi-unit neuron response recordings in central nucleus of IC. Of particular interest, we observe a significant reduction in cell labeling adjacent to the tonotopic bands, and suggest that such decreases represent inhibitory regions. C-fos-labeled bands and lateral regions of reduced labeling resemble excitatory and lateral-inhibitory response areas of IC neurons.

Time course of cochlear injury discharge (excitotoxicity) determined by ABR monitoring of contralateral cochlear events.

The dynamics of cochlear excitotoxicity can be monitored from effects on the contralateral ear. After unilateral mechanical ablation of the cochlea (in a mouse model) we observed immediate elevations in auditory brainstem evoked response (ABR) thresholds in the contralateral ear. Threshold elevations peaked at 2-3 h post ablation, and returned to baseline levels after 5-6 h. These contralateral effects are initiated by cochlear afferent injury discharges most likely activating the olivocochlear efferent system. Six hours after cochlear injury, ABR thresholds were fully returned to pre-lesion baseline levels and remained normal for up to 10 days of monitoring. We have confirmed that our cochlear ablation procedure increases short-term activity levels in the auditory brainstem and midbrain using c-fos labelling. The study provides insight into the dynamics of glutamate excitotoxicity, a pathological process directly related to acute tinnitus after acoustic trauma, and more generally implicated in many types of brain injury and neuro-degenerative disease.

Age related changes to the dynamics of contralateral DPOAE suppression in human subjects.

BACKGROUND: The two ears are linked with a neural pathway such that stimulation of one ear has a modulating effect on the contralateral cochlea. This is mediated by cochlear afferent neurons connecting with olivo-cochlear efferents. The monitoring of this pathway is easily achieved by measuring contralateral suppression of otoacoustic emissions, and there is some clinical value in the ability to assess the integrity of this pathway. An important step in an evaluation of clinical utility is to assess any age-related changes. Accordingly, in the present study we measure the dynamics of contralateral DPOAE suppression in a population of normal hearing subjects of different ages. METHODS: Using a real-time DPOAE recording method we assessed contralateral DPOAE suppression in 95 ears from 51 subjects (age range 2-52 years). DPOAE (2f1-f2; f2 = 4.4 kHz; f2/f1 = 1.22) input-output functions were measured. In response to contralateral broadband noise, dynamic aspects of DPOAE suppression were measured, specifically suppression onset latency and time constants. RESULTS: An age-related reduction in DPOAE amplitudes was observed. Both the detectability and the degree of contralateral DPOAE suppression were decreased in older age groups. We find an age-related increase in the latency of onset of DPOAE suppression to contralateral stimulation, but no significant change in suppression time-constants. CONCLUSION: Olivo-cochlear function as revealed by contralateral suppression of DPOAEs shows some important age-related changes. In addition to reduced emissions (outer haircell suppression) we find an increased latency that may reflect deterioration in auditory brainstem function. Regarding clinical utility, it is possible that the changes observed may reflect an aspect of age-related hearing loss that has not been previously considered.

Contralateral ear occlusion for improving the reliability of otoacoustic emission screening tests.

Newborn hearing screening is an established healthcare standard in many countries and testing is feasible using otoacoustic emission (OAE) recording. It is well documented that OAEs can be suppressed by acoustic stimulation of the ear contralateral to the test ear. In clinical otoacoustic emission testing carried out in a sound attenuating booth, ambient noise levels are low such that the efferent system is not activated. However in newborn hearing screening, OAEs are often recorded in hospital or clinic environments, where ambient noise levels can be 60-70 dB SPL. Thus, results in the test ear can be influenced by ambient noise stimulating the opposite ear. Surprisingly, in hearing screening protocols there are no recommendations for avoiding contralateral suppression, that is, protecting the opposite ear from noise by blocking the ear canal. In the present study we have compared transient evoked and distortion product OAEs measured with and without contralateral ear plugging, in environmental settings with ambient noise levels <25 dB SPL, 45 dB SPL, and 55 dB SPL. We found out that without contralateral ear occlusion, ambient noise levels above 55 dB SPL can significantly attenuate OAE signals. We strongly suggest contralateral ear occlusion in OAE based hearing screening in noisy environments.